Dyskinesia in Parkinson's Disease (Study P04501)

NCT00406029 | Completed Phase 2 Results DMC

• 2 other identifiers: P04501MK-3814-013
• Study Type: interventional
• Target: 253
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of the study is to assess the efficacy and safety of a range of doses of SCH 420814 (preladenant) when used together with a stable dose of L-dopa/dopa decarboxylase inhibitor to treat Parkinson's disease. In this study, we will be comparing 3 doses (1 mg, 2 mg, and 5 mg taken twice a day) of preladenant with placebo (sugar pill). Following an Interim Analysis (temporary hold for new enrollment-ongoing subjects will continue on treatment) to review drug safety, a new dose group of 10 mg (taken twice a day) may be added. Approximately 160 participants will be randomized in this study in approximately 22 study centers worldwide for the first part of this study. Following the Interim Analysis, 40 new participants may be added, for a total of 200 participants. The study is double blind, which means neither you nor your study doctor will know whether you are receiving the study medication or placebo.

Conditions

Parkinson Disease; Movement Disorders; Central Nervous System Diseases; Neurodegenerative Diseases; Brain Diseases

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Endpoint of 12 Weeks in the 3-day Average of Awake Time Per Day Spent in the "Off" State

  "Off" time refers to periods of inadequate control of Parkinson disease symptoms (worsening or presence of symptoms). For baseline and the 12 weeks treatment period, hours spent in the "off" state during awake time were recorded in half-hour time intervals using a daily diary at least 3 full days before scheduled visits. For baseline, the 24-hour average over 3 consecutive days was derived for Week -1. For endpoint, the 24-hour average was derived for the last available 3 consecutive days with postbaseline data available during the treatment period. Change from baseline in least squares (LS) means and pooled standard deviation (SD) were obtained from an analysis of covariance (ANCOVA) model with effect for treatment and baseline covariate. A negative change from baseline signifies less time spent in the "off" state.

  Baseline (Week -1) and up to 12 weeks

Secondary Outcomes (18)

• Change From Baseline in Awake Time Per Day Spent in the "Off" State at Each Visit

  Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12

• Change From Baseline in Awake Time Per Day Spent in the "on" State

  Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12

• Change From Baseline in Awake Time Per Day Spent in the "on" State (no Dyskinesias)

  Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12

• Change From Baseline in Awake Time Per Day Spent in the "on" State (With Troublesome Dyskinesias)

  Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12

• Change From Baseline in Awake Time Per Day Spent in the "on" State (Without Troublesome Dyskinesias)

  Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12

Study Arms (5)

Preladenant 1 mg BID

EXPERIMENTAL

Participants received preladenant 1 mg twice daily (BID) during the 12-week treatment period.

Drug: Preladenant; Drug: L-dopa; Drug: Other Parkinson's Disease treatments

Preladenant 2 mg BID

EXPERIMENTAL

Participants received preladenant 2 mg BID during the 12-week treatment period.

Drug: Preladenant; Drug: L-dopa; Drug: Other Parkinson's Disease treatments

Preladenant 5 mg BID

EXPERIMENTAL

Participants received preladenant 5 mg BID during the 12-week treatment period.

Drug: Preladenant; Drug: L-dopa; Drug: Other Parkinson's Disease treatments

Preladenant 10 mg BID

EXPERIMENTAL

Participants received preladenant 10 mg BID during the 12-week treatment period.

Drug: Preladenant; Drug: L-dopa; Drug: Other Parkinson's Disease treatments

Placebo BID

PLACEBO COMPARATOR

Participants received preladenant matching placebo BID during the 12-week treatment period.

Drug: Placebo; Drug: L-dopa; Drug: Other Parkinson's Disease treatments

Interventions

Preladenant DRUG

1 mg BID capsules

Also known as: SCH 420814

Preladenant 1 mg BID

Placebo DRUG

BID capsules

Placebo BID

L-dopa DRUG

Participants must receive L-dopa as part of their usual ongoing treatment for Parkinson's Disease. L-dopa is often administered concomitantly with a dopa decarboxylase inhibitor (e.g., carbidopa).

Placebo BID; Preladenant 1 mg BID; Preladenant 10 mg BID; Preladenant 2 mg BID; Preladenant 5 mg BID

Other Parkinson's Disease treatments DRUG

Participants may also receive other drugs as part of their usual ongoing treatment for Parkinson's Disease, such as dopamine agonists (e.g., pramipexole) and/or the catechol-O-methyl transferase (COMT) inhibitor entacapone.

Placebo BID; Preladenant 1 mg BID; Preladenant 10 mg BID; Preladenant 2 mg BID; Preladenant 5 mg BID

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be 30 years of age, of either sex and of any race, with a diagnosis of moderate to severe idiopathic Parkinson's disease for at least 5 years.
• Women of childbearing potential must have a negative serum pregnancy test at Visit 2 (Week -1). If participant is postmenopausal (not surgically induced), she must be postmenopausal by history for at least 2 years before study entry. If not, proper birth control must be used.
• Note: Acceptable methods of birth control include oral or injectable hormonal contraceptive, medically prescribed intrauterine device (IUD), and double-barrier method (eg, condom in combination with spermicide). Bilateral tubal ligation is an acceptable method of birth control for this study.
• Participants' clinical laboratory tests (complete blood count \[CBC\], blood chemistries, and urinalysis) must be within normal limits or clinically acceptable to the investigator/sponsor.

You may not qualify if:

• Participants with any form of drug-induced or atypical parkinsonism, cognitive impairment (Mini-Mental State Examination \[MMSE\] score \<=23), a history of Diagnostic and Statistical Manual of Mental Disorders IV (DSM IV) diagnosed major depression, unstable mild depression or psychosis, or participants taking tolcapone will be excluded. (Participants with mild depression who are well controlled on a stable dose of an antidepressant medication for at least 4 weeks before screening will be eligible.)
• All participants with a severe or ongoing unstable medical condition will be excluded including those with a history of poorly controlled diabetes, obesity associated with metabolic syndrome, uncontrolled hypertension, cerebrovascular disease, or any form of clinically significant cardiac disease, symptomatic orthostatic hypotension, renal failure, history of abnormal renal function, seizures, alcohol/drug dependence, or previous surgery for Parkinson's disease.
• Average daily consumption of more than two 4-oz (120 mL) glasses of wine or their equivalent.
• Because it is not known whether preladenant passes into breast milk and because the effects, if any, of preladenant on the developing human are unknown, women who are breastfeeding or who are considering breastfeeding are excluded from this trial.
• Participants with allergy/sensitivity to study drug or its excipients.
• Participants with any clinically significant condition or situation, other than the condition being studied that, in the opinion of the investigator, would interfere with the study evaluations or optimal participation in the study.
• Participants who have used any other investigational drugs within 30 days of Screening.
• Participants who are participating in any other clinical study.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Hauser RA, Cantillon M, Pourcher E, Micheli F, Mok V, Onofrj M, Huyck S, Wolski K. Preladenant in patients with Parkinson's disease and motor fluctuations: a phase 2, double-blind, randomised trial. Lancet Neurol. 2011 Mar;10(3):221-9. doi: 10.1016/S1474-4422(11)70012-6.

  PMID: 21315654 DERIVED

MeSH Terms

Conditions

Parkinson Disease; Movement Disorders; Central Nervous System Diseases; Neurodegenerative Diseases; Brain Diseases

Interventions

2-(2-furanyl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)-1-piperazinyl)ethyl)-7H-pyrazolo(4,3-e)(1,2,4)triazolo(1,5-c)pyrimidine-5-amine; Levodopa

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Nervous System Diseases; Synucleinopathies

Intervention Hierarchy (Ancestors)

Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2006
• First Posted: December 4, 2006
• Study Start: November 20, 2006
• Primary Completion: October 5, 2008
• Study Completion: November 3, 2008
• Last Updated: November 9, 2018
• Results First Posted: February 8, 2017

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share